Peripheral Immune Development in Premature Infants with and without NEC

标题： 患有和不患有NEC早产儿的外周免疫发育 摘要： 坏死性小肠结肠炎(NEC)是早产儿的一种破坏性并发症，经常导致死亡(20-20岁)。 50%)或严重的全身并发症。尽管NEC是一种多因素疾病，但其确切的病因仍在继续 很难被理解。因此，目前仍没有有效的预防方法或治疗方法。vt.给出 肠道和全身炎症增加见于NEC，很可能是免疫调节失调 系统因素在其发病机制中起作用。为了更好地了解NEC的发病机制，有必要 对早产儿出生后头两个月的正常免疫发育有扎实的了解 婴儿。我们从胎儿、NEC患者和对照组获得的初步数据显示， 肠道组织中总的和组织驻留的记忆T细胞急剧减少，T细胞增加 外围。此外，NEC与促炎巨噬细胞的显著增加有关。 肠道组织，并伴随循环单核细胞的减少。最近的工作已经开始解决如何 新生儿会产生外周免疫功能。然而，有关早产儿外周免疫发育的数据 婴儿出生后的头两个月是稀少的。因此，这一探索性提案的目标是明确 早产儿出生前两个月的正常免疫发育及其特征 NEC患者的调节失调。这一提议的首要假设是， 早产儿外周免疫系统先天免疫与获得性免疫的差异 与足月儿的隔室不同，正是这种差异使他们容易感染NEC。AS 早产儿的血容量是有限的，我们已经开发了一种方法来进行深度 使用飞行时间质谱仪(CyTOF)对低至100微升的血液进行免疫表型分析。这个独一无二的 方法论将使我们能够解决这一假设，目的如下：1)定义外周免疫 早产儿在出生后头两个月的发育情况(32周)。我们将对以下对象执行CyTOF 采集50例早产儿0周、1周、2周、4周、8周的外周血。深沉 免疫细胞格局的特征和主要细胞的发育轨迹图 早产儿的血统将会产生。2)识别相关的外周免疫细胞异常 随着NEC的发展。我们将确定免疫群体轨迹的失调，具体到 患NEC的早产儿。这些信息将为我们提供免疫细胞的模型 NEC易感性的潜在机制。该项目将是对 患有和不患有NEC的早产儿在头两个月的免疫系统发育情况， 并将为大规模深入研究其潜在的机制提供足够的数据 NEC的发展。

Title: Peripheral Immune Development in Premature Infants with and without NEC Abstract: Necrotizing enterocolitis (NEC) is a devastating complication of prematurity that frequently results in death (20- 50%) or severe systemic complications. Although NEC is a multifactorial disease, its precise etiology continues to be poorly understood. As such, there are still no effective prevention methods or treatments available. Given increased intestinal and systemic inflammation seen in NEC, it is likely that the dysregulation of the immune system contributes to its pathogenesis. In order to better understand NEC pathogenesis, it is essential to have a solid understanding of normal immune development that occurs over the first two months of age in premature infants. Our preliminary data obtained from fetuses, patients with NEC and control subjects, show that there is a drastic reduction of total and tissue resident memory T cells in the intestinal tissue and an increase in T cells in the periphery. Moreover, NEC is associated with a significant increase in pro-inflammatory macrophages in intestinal tissue, and a concomitant decrease in circulating monocytes. Recent work has begun to address how neonatal peripheral immunity develops. However, data on the peripheral immune development in premature infants over the first two months of life is sparse. Therefore, the goal of this exploratory proposal is to define normal immune development of premature infants over the first two months of life and characterize its dysregulation in patients with NEC. The overarching hypothesis of this proposal is that development of the peripheral immune system in preterm infants is different in the innate and adaptive immune compartments from that of term infants, and it is this difference that makes them susceptible to NEC. As the blood volume in premature infants is limited, we have developed a methodology to perform deep immunophenotyping on as little as 100 µliters of blood using mass cytometry time of flight (CyTOF). This unique methodology will allow us to address the hypothesis, with the following aims: 1) Define the peripheral immune development of premature infants (<32 weeks) over the first two months of life. We will perform CyTOF on peripheral blood from 50 premature infants, with samples collected at 0, 1, 2, 4, and 8 weeks. Deep characterization of the immune cell landscape and maps of the developmental trajectories of the major cell lineages in premature infants will be generated. 2) Identify peripheral immune cell abnormalities associated with the development of NEC. We will identify dysregulation of immune population trajectories specific to premature infants who develop NEC. This information will provide us with a model for the immune cell mechanism underlying susceptibility to NEC. This project would represent the first detailed deep examination of the development of the immune system in premature infants with and without NEC over the first two months, and will provide sufficient data for the development of a large-scale, in-depth study of the mechanism underlying the development of NEC.